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Fertility in Older Women

How does age affect fertility in the woman?

Most infertility specialists define an older woman as one who is more than 35 years, but this is an arbitrary number. A woman's fertility does not fall off at a particular age, but starts declining gradually after the age of 30. After 35, the drop is fairly dramatic; and after 38, it's even more so. However, there is no magic number at which fertility disappears and this decline is a progressive irreversible process.

In the past, it was assumed that as the woman got older, her entire reproductive system started failing. However, today we know that the uterus and the fallopian tubes remain relatively unaffected by age; and that the reason for the decline in fertility is the diminished number of eggs left in the ovary. Every girl is born with a finite number of eggs, and their number progressively declines with age. A measure of the remaining number of eggs in the ovary is called the "ovarian reserve"; and as the woman ages, her ovarian reserve gets depleted. The infertility specialist is really not interested in the woman's calendar (or chronological age), but rather her biological age - or how many eggs are left in her ovaries.

What are the tests for measuring ovarian reserve ?

Various tests have been described , to measure the ovarian reserve, so that we can determine which patients are good candidates for treatment. These tests are based on measuring the level of the FSH level in the blood; and include a basal ( day 3) FSH level. A high level suggests poor ovarian reserve; and a very high level is diagnostic of ovarian failure. A test that can provide earlier evidence of declining ovarian function is the clomiphene citrate challenge test ( CCCT). This is similar to a " stress test " of the ovary; and involves measuring a basal Day 3 FSH level; and a Day 10 FSH level , after administering 100 mg of clomiphene citrate from Day 5 to Day 9. If the sum of the FSH levels is more than 25, then this suggests poor ovarian function, and predicts that the woman is likely to have a poor ovarian response ( she will most probably grow few eggs, of poor quality) when superovulated. Another test which has been recently developed is the measurement of the level of the hormone, inhibin B , in the blood. Low levels of inhibin B ( which are produced by " good " follicles) suggests a poor ovarian reserve. However, just because a test result is normal does not mean that the quality or number of the eggs will be good - the final proof of the pudding is always in the eating !

The menopause is easy to define, because it is the point at which the menses cease, and at this time the eggs in the ovaries are finally depleted. However, the quality of eggs starts declining well before the menopause starts. Dr Jansen calls this the "oopause" - the time period before the menopause, during which fertility progressively declines because of deterioration in the quality of the eggs. This can manifest itself in many ways, some of which are extremely subtle, which is why the oopause can be so hard to identify. Initially, these women may present as having recurrent miscarriages, and then as having "unexplained infertility". While the number of eggs they grow seems fine initially, they do poorly in the IVF lab. Initially they may have unexplained implantation failure of apparently satisfactory embryos; and later, poor quality embryos; and then failure of fertilization.

What is the relationship between infertility and the midlife crisis ?

Infertility and the Midlife Crisis

Many women in their late 30s early 40s have postponed marriage or childbearing to obtain their education, establish themselves in careers, and become financially secure. These aspirations frequently have worked against the decision to have children. The passage of time, however, alters the way many women feel about motherhood by changing their perceptions about themselves as well as about the world around them. Additionally these changes may also have to do with having a new sense of maturity as well as a feeling of accomplishment. Thus, as women-and men-feel more secure about themselves, their feelings and ideas about children and parenthood may also change.

As a couple moves into midlife, they must also begin recognizing and coming to terms with their own mortality. For many, parenthood is a part of successfully completing an important stage in life. As couples begin to see and understand the passage of their own lives, the need to pass along life experiences to new generations enhances the meaning of life.

Men and women in midlife, who have made the decision to have children , may find to their dismay that they are frequently thwarted by the inability to conceive or by recurrent miscarriages. For women, the realities of the biologic clock cannot be overlooked. At this point, many couples are faced with dual crises which can compound their problems -infertility , as well as a midlife crisis - the developmental life changes that normally occur in the middle years. This is why we suggest that women who are more than 30 and who wish to postpone childbearing should get their FSH levels checked on Day 3 of their cycle. This is a simple blood test which allows the doctor to check your ovarian reserve ( the quantity and quality of the eggs in your ovaries). A high level suggests poor ovarian reserve and should be a wake-up alarm that your biological clock is ticking away rapidly. It's important that this test should be done in a reliable laboratory.

As women reach menopause, they begin to realize that the option of conceiving and bearing a child is closed to them. Just as the array of other life choices begins to narrow, the loss of this ability to choose to have a child can result in sadness and deep disappointment. The realization of this "missed opportunity" can also lead to self-recrimination and depression.

What are the fertility issues unique to older women ?

This is why the older woman presents a number of unusual personal problems. For one, most women can hear their own biologic clock ticking away loudly, and don't like being reminded about the fact that their age can be a limiting factor in their fertility. Moreover, many of these women are busy executives pursuing a career. They are very used to being successful, and find it difficult to come to terms with their biologic frailty. Because of all the media hype, they expect the assisted reproductive technologies to provide them with a quick answer.

However, few reports emphasise that pregnancy rates in older women, even with IVF, are only half of what they are with younger women - so that typically, a woman who is more than 40 years of age has a less than 10 % chance of having a live birth in an IVF cycle. Older women also find it much more difficult to get social support. Society can be both sexist and ageist, and most people feel it is "unnatural" for an older women to want to try to get pregnant.

The major problem for the older woman is that time is at a premium ! She simply cannot afford to waste her precious time on ineffective treatments; and it is better for her to move on to IVF sooner rather than later !

Older women present doctors with many challenging problems. For one, they usually respond poorly to ovarian stimulation, and pregnancy rates with treatment are lower. They also have an increased risk of having a miscarriage - and in women over 41 years of age, this risk can be as much as 50%! Moreover, as a woman ages, she has an increased risk of having medical problems in her pregnancy, because of preexisting medical problems such as diabetes and hypertension.

An especially thorny issue is the increased risk of birth defects because of aging eggs. As eggs get older, they have an increased risk of harbouring chromosomal errors, and this increases the risk of the baby having a chromosomal error, such as trisomy 21 (Down syndrome). Most clinics will offer prenatal diagnosis (such as chorion villus sampling, and amniocentesis ) to these women to screen for birth defects during pregnancy - but since some of these procedures increase the risk of a miscarriage, the couple often find themselves on the horns of a dilemma - and it is hard for them to decide whether to do the test or not to.

What is the oldest age at which an infertility specialist should accept a woman for treatment ?

Is there a particular age at which a woman should be denied treatment ? If so, then why ? and what should this age be ? and who should decide ? " Menopausal mums" have grabbed much media attention, and have raised a number of controversies - which still remain unresolved.

Much research is going on to try to increase the pregnancy rates after IVF in older women. One high tech option is to screen the embryos for aneuploidy (an abnormality in chromosomal number) using FISH (fluorescent in situ hybridisation) for preimplantation genetic diagnosis, a technique in which embryos are biopsied and their chromosomes analysed using probes. If only chromosomally normal, healthy embryos are transferred back, then many researchers feel that embryo implantation rates and pregnancy rates will be higher. Another option is assisted zona hatching, using chemicals or a laser, to create an opening in the zona (shell ) of the embryo. Scientists feel that this technique can allow the embryo to " hatch " and thus escape from the zone and implant into the uterine lining more easily. Some IVF clinics with advanced facilities, such as our represented ones, now offer these advanced techniques on a routine basis.

For older woman with a persistently poor ovarian response, many options have been explored to try to improve the number of eggs produced. This includes using supplemental growth hormone ; and the newer recombinant gonadotropins. However, the results of these have been disappointing, and the fact remains that we do not have an effective method of helping poor ovarian responders.

How can donor eggs help the older infertile woman ?

A very effective option for older woman whose own eggs do not grow well is that of using donor eggs or donor embryos. However, this is obviously a very sensitive emotional issue, and each couple needs to make their own decision. While using donor eggs and embryos does dramatically improve pregnancy rates, it is often an option many couples find hard to come to terms with.

It is also becoming increasingly difficult to find suitable egg donors. While egg donation has become commercialised in USA, this has raised a lot of hue and cry, because critics feel that young women are being enticed to "sell their eggs". Finding altruistic egg donors is an uphill task for most women, because they are often very reluctant to ask for help, since this would involve telling others about their problem.

Support groups like NEEDS (National Egg and Embryo Donation Society) in the UK have been very helpful in motivating voluntary egg donors by creating public awareness of the need for healthy young women to donate their eggs. Clinics have also adopted various approaches to help resolve this problem. Some large clinics run successful anonymous egg donation programs; others use known egg donors (either paid or unpaid); and others encourage their patients to share their supernumerary eggs (often for a financial consideration) with other patients.

An exciting option for the future may be that of egg banking. A lot of research is being focussed on developing more efficient methods to cryopreserve and store eggs. If this becomes clinically practicable, then it may become possible to freeze a woman's eggs or ovarian tissue when she is young, and store these for her in liquid nitrogen at -196 C, so that she can use her own "young" eggs in the future, whenever she decides to start her family !